Transgenic Mouse Core Facility Shared Resource: Project Summary Biology Shared Resource Group The ability to introduce foreign genes into the mammalian germ line or to selectively ablate endogenous genes from the mouse or rat genome, has proven to be one of the most powerful experimental tools available for understanding specific genetic requirements for tumor promoting regulatory pathways. In the area of oncology, transgenic mouse models have revealed the molecular pathways by which proto-oncogenes predispose cells to develop malignant tumors or how tumor suppressor genes maintain normal growth control. Transgenic strategies have also revolutionized the way we approach the complex problems associated with carcinogenesis, including the development of novel therapeutic intervention strategies. To support cancer research and utilization of this powerful technology, the Purdue University Center for Cancer Research (PCCR) Transgenic Mouse Core Facility Shared Resource (TMCF-SR) was established in 1998 through the generous support of the NCI and from funds obtained from the Purdue Office of the Vice President for Research. Since then, transgenic and gene targeted mouse models produced by the TMCF-SR have had a significant impact on the research that has been performed within the PCCR. In 2013 alone, the broad range of services provided by the TMCF-SR supported the research of 10 investigators from the Cell Identity and Signaling (CIS) Research Program, and from 2010-2013, TMCF-SR support has contributed to over 54 PCCR publications. The PCCR's TMCF Shared Resource is a state-of-the-art facility that offers a large number of services to the Center membership, including the creation of transgenic and knock-out mouse and rat models for gain-of- function and loss-of-function experimental approaches to dissect transcriptional, signaling, and environmental influences on tumor initiation, progression and metastasis. Model systems based on transgenic and knock- in/knock-out strategies provide approaches that are developmentally, anatomically and physiologically relevant to human disease, and that can supplement traditional xenograft models for testing new anti-cancer therapies. Transgenic animal models provide valuable reagents for studying aspects of cancer cell biology, ranging from the regulatory mechanisms governing gene expression patterns to cell-cell interactions, cell cycle control and regulation of signal transduction pathways. Additionally, these models have been instrumental in dissecting the importance of immune cells and stromal infiltrates to tumor progression, and have helped to identify novel cancer stem cell lineages that are often resistant to conventional chemotherapeutics.